NL7810275A - METHOD FOR PREPARING A MICROBICIDE PREPARATION - Google Patents

Description

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Applicant: Th. Goldschmidt AG in Essen,

Federal Republic of Germany

Short designation: Process for the preparation of a microbicidal preparation 1 The Dutch patent application 7601827 relates to quaternary imidazolium salts with the general formula 1 of the formula sheet, in which R 1 is a straight chain alkyl radical with 8-18 carbon atoms, 2 R an alkyl radical straight chain with 1 to 3 carbon atoms, 3 R represents a straight chain alkyl radical with 8 to 16 carbon atoms, and 10 X represents a chlorine or bromine atom.

. Said patent application further relates to a process for preparing said compounds in a manner known for analogous compounds, preferably in that a compound having the general formula 2 of the formula sheet, in which R and R have the above meanings, in a polar solvent with at least an equimolecular amount of a compound of the general formula RX, wherein R and X have the above meanings, react at temperatures between 80 and 150 ° C and then remove the solvent and any excess RX .

Finally, the said patent application also relates to a microbicidal preparation, consisting of one or more compounds of the above formula 1 and conventional formulating agents.

The aforementioned patent application discloses that the compounds mentioned therein are surprisingly very effective against bacteria, fungi and yeasts.

These compounds are soluble in water and can moreover be made up in the usual manner. Under confec- 7810275 t? -2 - "λ.

In this connection, ionization is understood to mean the preparation of preparations suitable for use, for example the preparation of aqueous solutions of the compounds of the invention in concentrated or ready-to-use concentrations.

The preparation also includes the creation of a certain pH value adapted to the application purpose, optionally the addition of cationic or non-ionic known surfactants in order to reduce the interfacial tension of the solutions and / or the cleaning agents. increase its action and possibly coloring and / or perfuming the preparation. Another form of preparation consists in preparing a dry product by using the pure crystalline substance or by mixing the pure substance with carriers, in particular inorganic inert substances. Recently, the dissolution of the active substances in low-boiling solvents and the spraying of these solutions of the active substances by means of a propellant have also gained importance. These preparations are marketed as aerosols.

As described above, cationic or non-ionic surfactants can be added to the compounds according to the invention. Suitable cation-active compounds are, for example, quaternary ammonium compounds, such as cetylpyridinium chloride or a large number of known benzalkonium chlorides.

As nonionic compounds known per se addition products of ethylene oxide to compounds with acid hydrogen, in particular to alcohols with a chain length of 8-18 carbon atoms, can be used.

The optimum pH value for the application is in the weakly acidic to neutral range and ranges from about 4 to 8. It is preferred to use weak organic acids, preferably acetic acid, to achieve the desired pH value. However, polyvalent acids such as citric acid and lactic acid are also suitable.

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1 The definition of the alkyl radical as straight chain alkyl radical 3 with 8-18 carbon atoms, R as straight chain alkyl radical 2 with 8-16 carbon atoms and R as straight chain alkyl radical with 1-3 carbon atoms leaves a large number of possible combinations. Surprisingly, it has now been found that from this large number of combinations leading to compounds with microbicidal properties, a single compound exhibits a clearly high activity against bacteria, fungi and yeasts outside the scope of the activity, in particular also against spores. . Moreover, this compound is therefore also effective as an algicide. The high activity of this compound lies outside the scope of the properties to be expected according to the Dutch patent application 7601827.

The invention is therefore a choice invention and relates to the compound 1,3-Di-n-decyl-2-methyl-imidazolium chloride or bromide (the compound 3) and to a microbicidal composition consisting of said compound and conventional, confectioners already explained in the foregoing. In this connection, it was surprising that the chosen compound exhibits very pronounced sporicidal activity in addition to the unexpectedly high activity.

The compound 3 is prepared in a manner known per se as described in Dutch patent application 7601827, for example by reacting 1-decyl-25-2-methyl-imidazole in a polar solvent with at least an equimolecular amount of n-decyl chloride. ride or bromide at temperatures between 80 and 150 ° C and then removes the solvent and any excess n-decyl chloride or bromide. As a polar solvent, a lower aliphatic alcohol, for example isopropanol, is very suitable in addition to water.

When n-decyl chloride is used to prepare 1,3-di-n-decyl-2-methyl-imidazolium chloride, the active substance is obtained as a weak light brown powder with a softening point of 68 ° C and a purity of 95% . Recrystallization from acetic acid ethyl ester results in a 7810275 A * - 4 - & >> 1 chemically pure compound with a softening point of 82 ° C.

It is not important for the activity of the imidazolium salt according to the invention whether it is in the form of a chloride or bromide. The following comparative tests were carried out with the chloride.

The proof of the microbicidal activity is given in the Dutch patent application 7601827 in the form of tables, in which tables the results of tests with certain test strains at a predetermined pH value for the respective active substances depending on the concentration and the time. In order to provide a more clear overview of the patentability of the subject of this invention, the following description will deviate from this method and mention the limiting concentration of the activity at a certain duration of action.

A time of action of 10 minutes was chosen for practical application in the case of bacteria, fungi, yeasts and bacillus spores. The pH range of the active substance solutions tested is in the neutral range in all tests. The values determined thereby are representative, since the same results and in particular the same interrelations between the results are obtained even when the pH value is decreased or increased.

The compound of the invention 1,3-Di-n-decyl-25 2-methyl-imidazolium chloride or bromide (compound 3) was compared with the following compounds: 1.3-Di-n-octyl-2-methyl-imidazolium chloride (compound 4) 1.3- Di-n-dodecyl-2-methyl-imidazolium chloride (Comp. 5) l-dodecyl-3-n-octyl-2-methyl-imidazolium chloride (Comp. 6) * 30 a) Efficacy_2_view_yan_bacteria

The microbiological activity of the compounds to be tested is determined by a suspension test in accordance with the "Richtlinien der Deutschen Gesellschaft für Hygiene und Mikrobiologie e.V." (Gustav Fischer 35

Verlag, Stuttgart, 1972). As test germs, staphylo- 7810275-5 - '«; 1 coccus aureus, Escherichia coli, Proteus vulgaris and Pseudo monas aeruginosa used.

Table A. Results: 5 -: --------; -

Test strain Limit concentration of the activity in parts per million __ Compound _ _ 4 4 5 6 S. aureus 5 500 50 10 * E. coli 10 500 500 50 P. vulgaris 5 100 100 50 P. aeruginosa 10 1000 500 100 f 15 b) Activity_game_of_moulds_and yeasts

Analogous to the tests described under a), the microbiological activity is determined in accordance with the "Directives der Deutschen Gesellschaft für Hygiene und 20

Microbiology e.V. "determined by means of a suspension test.

As test germs, Penicillium expansum, Aspergillus flavus, Trichophyton mentagropytes, Microsporum gypseum, Candida albicans, Hansenula anomala and Geotrichum candidum are used.

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Table B. Results;

Test strain Limit concentration of the activity in parts per million. Compound _ 30 ........ I --- 3— 1 ~ y. I.. . 5 I .SL · P. expansum 10 500 500 100 A. flavus 100 1000> 1000 500 T. mentagrophytes 10 500 50 50 M. gypseum 10 5Ö 50 50 25 C. albicans 5 500 50 10 H. anomala 5 500 500 50 G candidum 1 100 10 10 7810275:

Ar. - 6 - b · 1 c) Activity_ten <_ODevere_of_scoring

Spores of Bacillus subtilis and Bacillus cereus are used as test germs. In order to prepare the spore suspension, two nutrient agar plates inoculated with the vegetative germs of B. subtilis and B. cereus are incubated at 37 ° C for 10 to 12 days. The corresponding vegetative germs are rinsed from the well-grown plates with 10 ml sterile distilled water each time and the resulting germ suspension is centrifuged. The sediment is washed 2 times with sterile distilled water and then taken up in 5 ml sterile distilled water. The germ suspensions B. subtilis and B. cereus thus obtained are treated in a water bath at 80 ° C for 30 minutes before killing the vegetative cells.

"With the spore suspensions with a germ density of 10 - 10 germs / ml thus obtained, the sporicidal activity of the compounds to be tested is determined by means of the generally known suspension test (see above under a) and bl.), Whereby the nutrient broth 3% Tween vD 80 and 0.3% lecithin is added to eliminate a sporio-static aftereffect. Tween 80 is a commercially available ethoxilized sorbitan oleic acid ester.

Table C. Results: - - - - - - - - - - - —...... ...... -. . __ - - 25 Test strain Limit concentration of the activity in parts per million

Compound 3 4 5 6 3Q B. subtilis 0.3 1.8 ^ 2 1.2 B. cereus 0.6> 2 ^ 2 1.6 d) Activity_ten_ogzichte_van_algen

Chlorella pyrenoidosa is used as a test strain.

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This algae strain is cultured in a mixture of air and carbon dioxide in 80 ml of a nutrient solution 7810275 3 * - 7 -% 1 with the following composition: 4.045 g KNO 3 2.340 g NaCl 0.110 g CaCl 2 5 1.235 g MgSO ^ 0.010 g MnCl2 0.007 g ZnSO2 2.220 g NaH2PO4 0.890 g Na2HPO4 10 0/020 g PeCl3 5 l distilled water.

After centrifugation of the developed algae from the nutrient solution, the algae sediment is taken up in 20 ml of sterile tap water.

200 ml of the respective dilution of the algicidal agent to be investigated are placed in a 250 ml beaker. Parallel to these tests, a test is carried out with 200 ml of sterile tap water. To the individual amounts of water with active substance and the sterile tap water, 1 ml of the cultured algae suspension is added each time and the mixture is then left to stand at room temperature for 21 days. After this time, the amount of algae formed in each of the beakers is isolated by filtration, dried and weighed analytically accurately. The algicidal activity of a substance is expressed in the form of growth inhibition and calculated as follows: growth inhibition = 100% - 100 in which: a = dry weight of inoculated algae in mg 0 (1 b = dry weight in mg of the algae grown in water without additives c = dry weight in mg of the algae grown in the algicidal composition.

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Sr 1 Table D. Results:

Compound Amount of active substance Growth remission in parts per million% 5 - - 3 2 32 4 67 8. 95 10 4 2 8 4 42 '8 73 5 2 0 15 4 6.

8 26 6 2 12 4 45 20 8 '65

These values show that the properties of the compound 3 in an unpredictable manner with regard to its spectrum of action differ in quantitative and qualitative respect from the compounds described in Dutch patent application 7601827. The criteria for a choice invention are therefore met.

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Claims (3)

1. Process for preparing a microbicidal composition by mixing a 1,2,3-trialkylimidazalium halide with a carrier, characterized in that the active substance is 1,3-Di-n-decyl-2-methyl- imidazolium chloride or bromide. Dosing units consisting of made-up, measured amounts of preparations prepared according to claim 1. 3. Process for preparing a trialkyl-imidazolium halide, characterized in that 1,3-Di-n-decyl-2-methyl-imidazolium chloride or bromide is prepared in a manner known for analogous compounds. 7810275